Uncommon hepatocellular carcinoma in a non-cirrhotic woman with chronic hepatitis B virus infection after medical assisted reproduction: A case report

doi:10.4251/wjgo.v18.i4.116955

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World Journal of Gastrointestinal Oncology

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Case Report

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Apr 15, 2026; 18(4): 116955
Published online Apr 15, 2026. doi: 10.4251/wjgo.v18.i4.116955

Uncommon hepatocellular carcinoma in a non-cirrhotic woman with chronic hepatitis B virus infection after medical assisted reproduction: A case report

Clelia Asero, Giuliana Ciappina, Maria Stella Franzè, Teresa Maltese, Salvatore Gruttadauria, Duilio Pagano, Daniele Lombardo, Alessia Pitrone, Cristina Musolino, Massimiliano Berretta, Irene Cacciola

Clelia Asero, Teresa Maltese, Daniele Lombardo, Cristina Musolino, Massimiliano Berretta, Irene Cacciola, Department of Clinical and Experimental Medicine, University of Messina, Messina 98124, Sicilia, Italy

Clelia Asero, Maria Stella Franzè, Irene Cacciola, Medicine and Hepatology Unit, Department of Medical Science, University Hospital of Messina, Messina 98124, Sicilia, Italy

Giuliana Ciappina, Department of Medical Sciences, Section of Experimental Medicine, University of Ferrara, Ferrara 44121, Emilia-Romagna, Italy

Giuliana Ciappina, Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina 98166, Sicilia, Italy

Salvatore Gruttadauria, Duilio Pagano, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT, University of Pittsburgh Medical Center, Palermo 90127, Sicilia, Italy

Daniele Lombardo, Cristina Musolino, Division of Advanced Diagnostic Laboratories, University Hospital of Messina, Messina 98124, Sicilia, Italy

Alessia Pitrone, Division of Radiology, Department of Radiology and Radiotherapy, University Hospital of Messina, Messina 98124, Sicilia, Italy

Massimiliano Berretta, Division of Medical Oncology, University Hospital of Messina, Messina 98124, Sicilia, Italy

Author contributions: Cacciola I designed the research study, provided resources, cured visualization, and supervised the work; Cacciola I and Berretta M defined study methodology; Ciappina G performed the formal analysis; Asero C, Franzè MS, and Lombardo D contributed to investigation; Asero C, Pagano D, Pitrone A, Franzè MS, Lombardo D, and Musolino C were responsible for data curation; Cacciola I and Asero C prepared the original draft; Pagano D, Gruttadauria S, and Maltese T performed writing, review and editing. All authors have read and approved the final manuscript.

Supported by Ministero dell’Università e della Ricerca, No. PRIN_2022PNRR_P2022KCHLN_002 - CUP J53D23018010001 and No. PRIN_2022PNRR_P2022KCHLN_002 - CUP J43C22000310006 ID ECS00000022.

Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

Corresponding author: Irene Cacciola, MD, Professor, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 1, Messina 98124, Sicilia, Italy. icacciola@unime.it

Received: December 2, 2025
Revised: December 16, 2025
Accepted: February 28, 2026
Published online: April 15, 2026
Processing time: 130 Days and 19.7 Hours

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. It typically develops in patients with advanced chronic liver disease and only rarely occurs during pregnancy.

CASE SUMMARY

We report the case of a 46-year-old woman with HBeAg-negative chronic hepatitis B virus (HBV) infection, persistently low HBV DNA levels, and normal aminotransferase values, who developed HCC in a non-cirrhotic liver during a pregnancy achieved through assisted reproduction techniques. Antiviral therapy with Entecavir was initiated shortly before conception because of an increase in HBV DNA levels and was subsequently switched to Tenofovir during pregnancy. Despite a spontaneous miscarriage, alpha-fetoprotein levels continued to rise, prompting magnetic resonance imaging, which revealed a solitary hepatic nodule measuring 18 mm. The patient underwent hepatic resection, and histological examination confirmed a moderately differentiated HCC. Despite complete surgical resection, two early recurrences occurred within 15 months. Tumour and non-tumour liver tissues were collected intra-operatively, snap-frozen, and processed for molecular analyses to assess total HBV DNA, covalently closed circular DNA and HBV RNA levels.

CONCLUSION

HBV infection and pregnancy-related immunological imbalance may contribute to HCC development, underscoring the need for careful surveillance in HBsAg-positive women.

Keywords: Hepatocellular carcinoma; Chronic hepatitis B; Pregnancy; Reproductive techniques; Oestrogens; Case report

Core Tip: Hepatocellular carcinoma is rare during pregnancy and is associated with adverse outcomes for both the mother and the foetus. We report the case of a 46-year-old woman with HBeAg-negative chronic hepatitis B infection (HBV) who developed recurrent hepatocellular carcinoma after a pregnancy achieved through medically assisted reproduction. After surgical resection, immunofluorescence analysis of tumour samples showed no expression of oestrogen receptors, while molecular analyses performed on tumour and non-tumour tissues revealed high levels of total HBV DNA, HBV covalently closed circular DNA and HBV RNA, suggesting a virus-host interaction that may account for the aggressive behaviour of the neoplasm.